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| ID | Type | Description | Link |
|---|---|---|---|
| PACTR201907754270299 | Registry Identifier | Pan African Clinical Trials Registry |
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| Name | Class |
|---|---|
| Serum Institute of India Pvt. Ltd. | INDUSTRY |
| Medical Research Council Unit, The Gambia | OTHER |
| University College, London | OTHER |
| FHI 360 |
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The primary objectives of this study are to evaluate the immunogenicity (antibody response) and safety and tolerability of a 2-dose primary series and booster dose (2+1 schedule) of Pneumosil co-administered with routine pediatric vaccines in healthy infants in The Gambia.
This study will provide data necessary to evaluate the safety and immunogenicity of Pneumosil when administered in an alternative schedule to the 3 dose primary schedule (3+0) evaluated in the Phase 3 pivotal trial (VAC-056; NCT03197376) - namely in a 2 dose primary and booster (2+1) schedule - and compare immunogenicity to that of both currently licensed second-generation pneumococcal conjugate vaccines (Synflorix and Prevenar 13) administered in the same 2+1 schedule.
In this prospective, single center, randomized, active-controlled, observer-blind, Phase 3 descriptive study, 660 healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve infants will be randomized 1:1:1 to receive 3 doses of either Pneumosil, Synflorix or Prevenar 13 at 6 weeks, 14 weeks and 9-10 months of age. Standard Expanded Program on Immunization (EPI) vaccinations in The Gambia will be given concomitantly with all 3 doses of study vaccine.
The booster vaccination window was extended up to 18 months of age due to a pause in the study due to the coronavirus disease 2019 (COVID-19) pandemic. The study schedule for participants is as follows:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pneumosil | Experimental | Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
|
| Synflorix | Active Comparator | Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
|
| Prevenar 13 | Active Comparator | Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pneumosil | Biological | One single dose contains 2 μg of polysaccharide for serotypes 1, 5, 6A, 7F, 9V, 14, 19A, 19F and 23F, and 4 μg for serotype 6B formulated with aluminium phosphate as an adjuvant in an appropriate buffer |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples collected 4 weeks after the booster dose (Visit 6). The pneumococcal serotype-specific IgG ELISAs were performed using the World Health Organisation (WHO) reference assay at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, United Kingdom (UK), where the assay was validated. | 4 weeks post booster dose |
| Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination | Solicited local reactions included tenderness, erythema/redness and induration/swelling at the study vaccine injection site. Solicited systemic reactions included cutaneous rash, fever (based on axillary temperature), irritability, drowsiness, and decreased appetite. The severity of all solicited AEs was graded from mild (Grade 1) to potentially life threatening (Grade 4), based on protocol-defined criteria that were derived from Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 2.0, November 2014). | Day 0 to Day 6 after each vaccination |
| Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs) | AEs include any intercurrent illness or injury during the study, clinically significant worsening of a preexisting condition, and any solicited AE that occurred or was ongoing 6 days after study vaccine administration. A TEAE is an event that was not present prior to administration of the study vaccine, or increased in intensity after administration of the study vaccine. Unsolicited AEs were graded using the scale below: Grade 1: Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2: Moderate; minimal, local, or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Related AEs are AEs where the Investigator determined a reasonable causal relationship between the vaccine administered and the AE based on medical judgement. |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster | The functional activity of the antibody response to the 10 serotypes contained in Pneumosil was determined in serum samples collected 4 weeks after the booster dose in a subset of 50 participants per group. This activity was determined using the 4-fold multiplexed opsonophagocytic assay (MOPA) developed at the University of Alabama at Birmingham, and performed at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, UK, where the assay was validated. A higher titer indicates increased antibody-mediated opsonophagocytosis. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ed Clarke, MB ChB, PhD | MRCG at LSHTM | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM) | Banjul | The Gambia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36638819 | Derived | Adigweme I, Futa A, Saidy-Jah E, Edem B, Akpalu E, Dibbasey T, Sethna V, Dhere R, Kampmann B, Bengt C, Sirr J, Hosken N, Goldblatt D, Antony K, Alderson MR, Lamola S, Clarke E. Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial. Lancet Infect Dis. 2023 May;23(5):609-620. doi: 10.1016/S1473-3099(22)00734-4. Epub 2023 Jan 10. |
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Eligible participants were randomized equally (in a 1:1:1 ratio), based on a pre-established randomization scheme, to receive either Pneumosil, Synflorix or Prevenar 13. Participants were to receive two primary vaccinations plus a booster vaccination at 9-10 months of age. The booster vaccination window was extended up to 18 months of age due to a pause in the study due to the COVID-19 pandemic; actual mean age of booster administration was 12.5 months and ranged from 9 to 16 months.
Healthy, Gambian male and female, pneumococcal conjugate vaccine (PCV)-naïve infants were screened and enrolled at the Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM).
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| ID | Title | Description |
|---|---|---|
| FG000 | Pneumosil | Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| FG001 | Synflorix | Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| FG002 | Prevenar 13 | Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pneumosil | Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| BG001 | Synflorix |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples collected 4 weeks after the booster dose (Visit 6). The pneumococcal serotype-specific IgG ELISAs were performed using the World Health Organisation (WHO) reference assay at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, United Kingdom (UK), where the assay was validated. | Primary Per Protocol Immunogenicity Population (PP_IMM) includes all randomized participants who received all 3 study vaccinations (including booster), contributed post-booster immunogenicity measurements, and with no major protocol deviations that were determined to potentially interfere with immunogenicity assessment. Participants with available data for each serotype are included in the analysis. | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | 4 weeks post booster dose |
|
All-cause mortality and SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall. Non-serious AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post booster vaccination; approximately 8.5 months overall.
Data reported Include both solicited and unsolicited events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pneumosil | Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Alderson | PATH | + 206.302.4859 | malderson@path.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 18, 2020 | Nov 11, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 6, 2021 | Nov 11, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011018 | Pneumonia, Pneumococcal |
| ID | Term |
|---|---|
| D011008 | Pneumococcal Infections |
| D013290 | Streptococcal Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
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| ID | Term |
|---|---|
| C538862 | 13-valent pneumococcal vaccine |
| C547294 | PHiD-CV vaccine |
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| OTHER |
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|
| Prevenar 13 | Biological | One single dose contains 2.2 µg of the following pneumococcal polysaccharides serotypes - 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F - and 4.4 µg of pneumococcal polysaccharide serotype 6B, all conjugated to CRM197 and absorbed onto aluminum phosphate |
|
| Synflorix | Biological | One single dose contains 1 μg of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14, and 23F, and 3μg of serotypes 4, 18C, and 19F formulated with aluminum phosphate as an adjuvant. |
|
|
| AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall. |
| Number of Participants With Serious Adverse Events (SAEs) | An SAE was a specific AE that:
| SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall. |
| 4 weeks post booster dose |
| Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose. | 4 weeks post booster dose |
| Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster | Seroresponse rate was also defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 1.0 μg/mL. The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose. | 4 weeks post booster dose |
| Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples taken 4 weeks after the booster vaccination. | 4 weeks post booster dose |
| Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose. | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
| Geometric Mean Concentration of Serotype-specific IgG Antibodies Four Weeks After Completion of Primary Vaccinations | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose. | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
| Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks After Completion of Primary Vaccinations | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA). | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
| Geometric Mean Titers of Serotype-specific Serum OPA Four Weeks After Primary Vaccinations | Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA). | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
| Percentage of Participants With Serotype-specific Serum IgG Concentrations ≥ 0.35 μg/mL Prior to Booster | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose. | Prior to the booster dose at approximately 9 to 16 months of age |
| Geometric Mean Concentration of Serotype-specific Serum IgG Antibodies Prior to Booster | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose. | Prior to the booster dose at approximately 9 to 16 months of age |
| Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Prior to Booster | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose. | Prior to the booster dose at approximately 9 to 16 months of age |
| Geometric Mean Titer of Serotype-specific Serum OPA Prior to Booster | Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose. | Prior to the booster dose at approximately 9 to 16 months of age |
| Ratio of Serotype-specific Serum IgG GMC 4 Weeks Post-Booster to Serotype-specific IgG GMC 4 Weeks After Completion of Primary Vaccinations | Booster response was measured by the ratio of IgG GMCs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations. | 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster |
| Ratio of Serotype-specific Serum OPA GMT 4 Weeks Post-Booster to Serotype-specific OPA GMT 4 Weeks After Completion of Primary Vaccinations | OPA booster response was measured by the ratio of OPA GMTs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations. | 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster |
| Adverse Event |
|
| Death |
|
| Other |
|
| Lost to Follow-up |
|
Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.
| BG002 | Prevenar 13 | Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| BG003 | Total | Total of all reporting groups |
| days |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Ethnicity | Count of Participants | Participants |
|
| Primary Cooking Fuel Source | Count of Participants | Participants |
|
| Primary Water Source for Cooking/Drinking | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Length | Mean | Standard Deviation | cm |
|
| OG000 | Pneumosil | Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| OG001 | Synflorix | Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
| OG002 | Prevenar 13 | Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. |
|
|
|
| Primary | Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination | Solicited local reactions included tenderness, erythema/redness and induration/swelling at the study vaccine injection site. Solicited systemic reactions included cutaneous rash, fever (based on axillary temperature), irritability, drowsiness, and decreased appetite. The severity of all solicited AEs was graded from mild (Grade 1) to potentially life threatening (Grade 4), based on protocol-defined criteria that were derived from Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 2.0, November 2014). | The Safety Analysis Set (Safety Population) included all participants who were randomized, received a study vaccination, and provided post-vaccination safety data. | Posted | Count of Participants | Participants | Day 0 to Day 6 after each vaccination |
|
|
|
| Primary | Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs) | AEs include any intercurrent illness or injury during the study, clinically significant worsening of a preexisting condition, and any solicited AE that occurred or was ongoing 6 days after study vaccine administration. A TEAE is an event that was not present prior to administration of the study vaccine, or increased in intensity after administration of the study vaccine. Unsolicited AEs were graded using the scale below: Grade 1: Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2: Moderate; minimal, local, or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Related AEs are AEs where the Investigator determined a reasonable causal relationship between the vaccine administered and the AE based on medical judgement. | Safety analysis set | Posted | Count of Participants | Participants | AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall. |
|
|
|
| Primary | Number of Participants With Serious Adverse Events (SAEs) | An SAE was a specific AE that:
| Safety analysis set | Posted | Count of Participants | Participants | SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall. |
|
|
|
| Secondary | Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster | The functional activity of the antibody response to the 10 serotypes contained in Pneumosil was determined in serum samples collected 4 weeks after the booster dose in a subset of 50 participants per group. This activity was determined using the 4-fold multiplexed opsonophagocytic assay (MOPA) developed at the University of Alabama at Birmingham, and performed at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, UK, where the assay was validated. A higher titer indicates increased antibody-mediated opsonophagocytosis. | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Geometric Mean | 95% Confidence Interval | titer | 4 weeks post booster dose |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose. | Primary Per Protocol Immunogenicity population with available serotype data | Posted | Number | 95% Confidence Interval | percentage of participants | 4 weeks post booster dose |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster | Seroresponse rate was also defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 1.0 μg/mL. The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the booster dose. | Primary Per Protocol Immunogenicity population with available data | Posted | Number | 95% Confidence Interval | percentage of participants | 4 weeks post booster dose |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples taken 4 weeks after the booster vaccination. | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Number | 95% Confidence Interval | percentage of participants | 4 weeks post booster dose |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG antibody concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose. | Primary Per Protocol Immunogenicity population with available serotype data | Posted | Number | 95% Confidence Interval | percentage of participants | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
|
|
|
| Secondary | Geometric Mean Concentration of Serotype-specific IgG Antibodies Four Weeks After Completion of Primary Vaccinations | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected 4 weeks after the second primary vaccination dose. | Primary Per Protocol Immunogenicity Population with available serotype data | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks After Completion of Primary Vaccinations | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA). | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Number | 95% Confidence Interval | percentage of participants | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
|
|
|
| Secondary | Geometric Mean Titers of Serotype-specific Serum OPA Four Weeks After Primary Vaccinations | Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA). | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Geometric Mean | 95% Confidence Interval | titer | 4 weeks after completion of primary vaccinations (at age 18 weeks) |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum IgG Concentrations ≥ 0.35 μg/mL Prior to Booster | The seroresponse rate was defined as the percentage of infants with serotype-specific IgG concentrations of at least 0.35 μg/mL, which is the reference concentration for assessment of vaccine efficacy against invasive pneumococcal diseases (IPDs). The IgG concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose. | Primary Per Protocol Immunogenicity population with available serotype data | Posted | Number | 95% Confidence Interval | percentage of participants | Prior to the booster dose at approximately 9 to 16 months of age |
|
|
|
| Secondary | Geometric Mean Concentration of Serotype-specific Serum IgG Antibodies Prior to Booster | The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by ELISA in serum samples collected immediately prior to the booster vaccination dose. | Primary Per Protocol Immunogenicity population with available serotype data | Posted | Geometric Mean | 95% Confidence Interval | μg/mL | Prior to the booster dose at approximately 9 to 16 months of age |
|
|
|
| Secondary | Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Prior to Booster | The OPA seroresponse rate was defined as the percentage of infants with an OPA titer of at least 8. Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose. | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Number | 95% Confidence Interval | percentage of participants | Prior to the booster dose at approximately 9 to 16 months of age |
|
|
|
| Secondary | Geometric Mean Titer of Serotype-specific Serum OPA Prior to Booster | Opsonophagocytic activity was measured using the 4-fold multiplexed opsonophagocytic assay (MOPA) from serum samples collected immediately prior to the booster vaccination dose. | Primary Per Protocol Immunogenicity population with available serotype data; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Geometric Mean | 95% Confidence Interval | titer | Prior to the booster dose at approximately 9 to 16 months of age |
|
|
|
| Secondary | Ratio of Serotype-specific Serum IgG GMC 4 Weeks Post-Booster to Serotype-specific IgG GMC 4 Weeks After Completion of Primary Vaccinations | Booster response was measured by the ratio of IgG GMCs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations. | Primary Per Protocol Immunogenicity population with available data for each serotype at both time points | Posted | Geometric Mean | 95% Confidence Interval | ratio | 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster |
|
|
|
| Secondary | Ratio of Serotype-specific Serum OPA GMT 4 Weeks Post-Booster to Serotype-specific OPA GMT 4 Weeks After Completion of Primary Vaccinations | OPA booster response was measured by the ratio of OPA GMTs measured at the post-booster visit to those measured 4 weeks after completion of primary vaccinations. | Primary Per Protocol Immunogenicity population with available data for each serotype at both time points; OPA assays were conducted on the first 50 samples from each treatment group. | Posted | Geometric Mean | 95% Confidence Interval | ratio | 4 weeks after completion of primary vaccinations (at age 18 weeks) and 4 weeks post booster |
|
|
|
| 1 |
| 220 |
| 12 |
| 220 |
| 212 |
| 220 |
| EG001 | Synflorix | Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. | 0 | 220 | 10 | 220 | 213 | 220 |
| EG002 | Prevenar 13 | Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age. | 1 | 220 | 7 | 220 | 211 | 220 |
| Bronchiolitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Periorbital cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Infected dermal cyst | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Meningitis bacterial | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Vulval cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Atrioventricular septal defect | Congenital, familial and genetic disorders | MedDRA (23.0) | Systematic Assessment |
|
| Dermoid cyst | Congenital, familial and genetic disorders | MedDRA (23.0) | Systematic Assessment |
|
| Sickle cell anaemia | Congenital, familial and genetic disorders | MedDRA (23.0) | Systematic Assessment |
|
| Incarcerated umbilical hernia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Intussusception | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Rash pustular | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Skin candida | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Body tinea | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Bronchiolitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Febrile infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Tinea capitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Tinea infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Cutaneous larva migrans | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Tinea versicolour | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Pustule | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Acarodermatitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Dysentery | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Infected dermal cyst | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Molluscum contagiosum | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Viral rash | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Angular cheilitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Breast abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Candida nappy rash | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Dermatophytosis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Gingival abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Helminthic infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Mastitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Periorbital cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site pustule | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
|
| Irritability postvaccinal | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site pain | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site induration | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site erythema | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vaccination site swelling | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Developmental delay | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA (23.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Diarrhoea haemorrhagic | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Infantile colic | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash vesicular | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Intertrigo | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pityriasis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Skin erosion | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
|
| Weight gain poor | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Infant irritability | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Skin laceration | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Eye injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Tooth injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
|
| Conjunctivitis allergic | Eye disorders | MedDRA (23.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (23.0) | Systematic Assessment |
|
| Vernal keratoconjunctivitis | Eye disorders | MedDRA (23.0) | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
|
| Pulmonary valve stenosis | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
|
| Cystic lymphangioma | Congenital, familial and genetic disorders | MedDRA (23.0) | Systematic Assessment |
|
| Hydrocele | Congenital, familial and genetic disorders | MedDRA (23.0) | Systematic Assessment |
|
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
|
| Balanoposthitis | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
|
Not provided
Not provided
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D018410 | Pneumonia, Bacterial |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
|
| Tenderness |
|
| Erythema/Redness |
|
| Induration/Swelling |
|
| Any systemic reaction |
|
| Any systemic reaction Grade 3 or higher |
|
| Fever |
|
| Fever Grade 3 or higher |
|
| Cutaneous Rash |
|
| Cutaneous Rash Grade 3 or higher |
|
| Irritability |
|
| Irritability Grade 3 or higher |
|
| Drowsiness |
|
| Drowsiness Grade 3 or higher |
|
| Decreased Appetite |
|
| Decreased Appetite Grade 3 or higher |
|
|
| Grade 1 TEAE |
|
| Vaccine-related Grade 1 TEAE |
|
| Grade 2 TEAE |
|
| Vaccine-related Grade 2 TEAE |
|
| Grade 3 TEAE |
|
| Vaccine-related Grade 3 TEAE |
|
| Grade 4 TEAE |
|
| Grade 5 TEAE |
|
| Vaccine related Grade 5 TEAE |
|
| TEAEs leading to study discontinuation |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Seroytpe 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|
| Serotype 5 |
|
|
| Serotype 6A |
|
|
| Serotype 6B |
|
|
| Serotype 7F |
|
|
| Serotype 9V |
|
|
| Serotype 14 |
|
|
| Serotype 19A |
|
|
| Serotype 19F |
|
|
| Serotype 23F |
|
|